The present invention relates generally to the noninvasive measurement of optically absorbing compounds in turbid media including concentrations of biochemically relevant compounds in tissue and, more particularly, to a method for noninvasively measuring absorption changes in tissue where the pathlength in the tissue of the collected photons is insensitive to changes in the scattering parameters of the tissue.
Noninvasive in vivo methods for measuring absorption coefficients of tissue are potentially useful biomedical tools. Applications include measurements of endogenous compounds such as hemoglobin, bilirubin, and cytochrome oxidase, as well as determining concentrations of exogenous chromophores such as photodynamic therapy and chemotherapy drugs. The specific case of chemotherapy drugs can be used to illustrate the potential benefits of a noninvasive or minimally invasive method for measuring local tissue concentrations. The therapeutic benefit of chemotherapy drugs is determined by the tissue concentration of the drug in the targeted site. The only minimally invasive measurement available to the oncologist is to track the blood-serum concentration and assume a particular relationship to the tissue concentration, which is generally unreliable. Spectroscopic investigation of tissue for concentrations of species is generally performed in reflectance. However, baseline variations in unprocessed spectra generally overwhelm the absorption spectral features. Reflectance values measured on different sites on the same person, or from the same site on different people, can differ substantially even when the absorber is present in the same concentration. The scattering coefficient of biological tissue depends on the concentration of interstitial water, the density of structural fibers, and the shapes and sizes of cellular structures, to name just three factors. Other methods for tracking pharmicokinetics locally, such as microdialysis, are invasive. Moreover, microdialysis measures only the intercellular fluid and provides no information about drug concentrations inside the cells, a key issue for chemotherapy agents. The ability to noninvasively track compound concentrations by examining changes in absorption that are due to the presence of the drug in the target tissue would be useful in clinical pharmacology, especially for the development of new drugs.
Most work to date has concentrated on making optical measurements, in a geometry for which the diffusion approximation is applicable, although neural-network and Monte Carlo analyses have been used to examine situations where the diffusion approximation does not hold. In xe2x80x9cOptimal Probe Geometry For Near-Infrared Spectroscopy Of Biological Tissue,xe2x80x9d by G. Kumar and J. M. Schmitt, Applied Optics 36, 2286 (1997), the authors discuss the influence of probe geometry on spectroscopic absorption measurements obtained from the surface of turbid biological tissue. Basically, a source of light and a detector for backward scattered light are placed in close proximity to each other on the surface of the tissue to be investigated. In particular, although the choice of probe design is commonly dictated by commercial availability rather than by optimization, it was found that a range of probe spacings exists in which scattering variations have the least effect on fluence measurements. In addition, by choosing the separation between the source and detector probes (for small-diameter fibers) to be between 2 and 5 mm, Kumar and Schmitt have minimized the sensitivity of the detected fluence to the ratio of the fractional sensitivities, to the reduced scattering coefficients, xcexcsxe2x80x2, and to the absorption coefficient, xcexca, for anisotropically scattering biological tissue with scattering coefficients in the range between 0.5 and 1.5 mmxe2x88x921. Kumar and Schmitt suggest that this also improves the accuracy of absorption measurements made on such tissues. Kumar and Schmitt, however, do not teach either theoretically or experimentally that maximizing the ratio of the fractional sensitivities to xcexcsxe2x80x2 and xcexca optimizes the accuracy of measurements of xcexca.
Accordingly, it is an object of the present invention to provide an apparatus for spectroscopically measuring absorption of target species in turbid media where the pathlength traveled by the collected light through the medium is minimally dependent on the scattering parameters of the medium, such that small changes in absorption can be measured independent of variations in scattering.
Additional objects, advantages and novel features of the invention will be set forth in part in the description that follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
To achieve the foregoing and other objects, and in accordance with the purposes of the present invention, as embodied and broadly described herein, the apparatus for measuring absorption of light by a material in a small volume of highly scattering medium of this invention may include: a source of light having a wavelength which is absorbed by the material; a first optical fiber for receiving the light and directing it onto the surface of the medium, such that the light enters the medium; a second optical fiber located a chosen distance from the first optical fiber on the surface of the highly scattering media for collecting and receiving a portion of the light scattered from the medium in a direction opposite to the direction of the light entering the medium; and a light detector for detecting light exiting the second optical fiber, whereby the distance between the first optical fiber and the second optical fiber is chosen such that the dependence of the pathlength of the light entering the medium taken to reach the second fiber on the scattering parameters of said highly scattering medium is minimized, and a measurement of the light absorbed by a portion of the material is obtained.
Preferably, the chosen distance between the first optical fiber and the second optical fiber on the surface of the medium is about 1.7 mm.
It is also preferred that the diameter of the first optical fiber and the diameter of the second optical fiber are less than 400 xcexcm.
Preferably also, the second end of the first optical fiber and the first end of said second optical fiber are placed in direct optical contact with the highly scattering material in order that surface reflections are minimized and that all of the collected light has undergone multiple scattering through the highly scattering material.